title: MicroRNA-301 mediates proliferation and invasion in human breast cancer.
abstract: Several microRNAs have been implicated in human breast cancer but none to date have been validated or utilized consistently in clinical management. MicroRNA-301 (miR-301) overexpression has been implicated as a negative prognostic indicator in lymph node negative (LNN) invasive ductal breast cancer, but its potential functional impact has not been determined. Here we report that in breast cancer cells, miR-301 attenuation decreased cell proliferation, clonogenicity, migration, invasion, tamoxifen resistance, tumor growth, and microvessel density, establishing an important oncogenic role for this gene. Algorithm-based and experimental strategies identified FOXF2, BBC3, PTEN, and COL2A1 as candidate miR-301 targets, all of which were verified as direct targets through luciferase reporter assays. We noted that miR-301 is located in an intron of the SKA2 gene which is responsible for kinetochore assembly, and both genes were found to be coexpressed in primary breast cancer samples. In summary, our findings define miR-301 as a crucial oncogene in human breast cancer that acts through multiple pathways and mechanisms to promote nodal or distant relapses.
authors.affiliation: Department of Medical Biophysics, Ontario Cancer Institute, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Kate
authors.initials: K
authors.lastname: Gerster
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
authors.forename: Jasmine
authors.initials: J
authors.lastname: Tsang
authors.forename: Levi
authors.initials: L
authors.lastname: Waldron
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Angela B
authors.initials: AB
authors.lastname: Hui
authors.forename: Jenna
authors.initials: J
authors.lastname: Sykes
authors.forename: Christine
authors.initials: C
authors.lastname: P'ng
authors.forename: Naomi
authors.initials: N
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: McCready
authors.forename: Anthony
authors.initials: A
authors.lastname: Fyles
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D013629:Tamoxifen / Q000627:therapeutic use; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; C499177:COL2A1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D024043:Collagen Type II; C486413:FOXF2 protein, human; D051858:Forkhead Transcription Factors; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C516428:SKA2 protein, human; D013629:Tamoxifen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human